title: Phagocytic microglial phenotype induced by glibenclamide improves functional recovery but worsens hyperalgesia after spinal cord injury in adult rats.
abstract: Microglial cell plays a crucial role in the development and establishment of chronic neuropathic pain after spinal cord injuries. As neuropathic pain is refractory to many treatments and some drugs only present partial efficacy, it is essential to study new targets and mechanisms to ameliorate pain signs. For this reason we have used glibenclamide (GB), a blocker of KATP channels that are over expressed in microglia under activation conditions. GB has already been used to trigger the early scavenger activity of microglia, so we administer it to promote a better removal of dead cells and myelin debris and support the microglia neuroprotective phenotype. Our results indicate that a single dose of GB (1 μg) injected after spinal cord injury is sufficient to promote long-lasting functional improvements in locomotion and coordination. Nevertheless, the Randall-Selitto test measurements indicate that these improvements are accompanied by enhanced mechanical hyperalgesia. In vitro results indicate that GB may influence microglial phagocytosis and therefore this action may be at the basis of the results obtained in vivo.
authors.affiliation: Group of Neuroplasticity and Regeneration, Institut de Neurociències and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), E-08193, Bellaterra, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Redondo-Castro
authors.forename: Joaquim
authors.initials: J
authors.lastname: Hernández
authors.forename: Nicole
authors.initials: N
authors.lastname: Mahy
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005905:Glyburide / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D008124:Locomotion; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010587:Phagocytosis; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D014110:Touch
chemical_list: D018696:Neuroprotective Agents; D005905:Glyburide
keywords: electrophysiology; functional recovery; microglia; neuropathic pain; spinal cord injury